The safety of diagnostic ultrasound has not been established. To provide information useful for risk-evaluations and for planning future experiments, we propose to explore the biological effects of several types of diagnostic ultrasound (linear, sector, Doeppler-pulsed and continuous) on mammalian genes, chromosomes, and early embryos. Five in vitro biological assays will be used: 1) sister chromatid exchange frequencies in lymphocyte cultures; 2) cell-cycle times in human lymphocytes and fetal fibroblasts; 3) transformation rates in baby hamster kidney cell cultures; 4) frequencies of gene mutation at the HGPRT locus in cultured human foreskin fibroblasts; 5) teratogenesis in preimplantation mouse embryos. We will 1) construct a new in vitro exposure apparatus, 2) insure that ultrasound exposures delivered to the biological assay systems (cells and blastocysts) are representative of those delivered to the biological assay systems (cells and blastocysts) are representative of those delivered clinically to the human fetus or ovary, and that ultrasound monitoring experiments of the "dose" delivered is feasible and accurate, 3) expose various human and hamster cultured cells, and mouse blastocysts, to each of four types of ultrasound machines used clinically. Four different times will be tested to determine if there is a "dose" response. The philosophy regarding quantifying exposure is that the physical measurements made may be global in nature so that any reasonable methodology for computing a numerical exposure can be subsequently applied to the physical data for each experiment. Evidence for an ultrasound effect would be a) an increase in siser chromatid exchange frequencies; b) an alteration of cell cycle parameters; c) an increase in frequency of transformation; d) an increase in mutation rate; e) an increase in fetal loss or rate of congenital malformations. We will also conduct pilot studies on the synergistic effects between ultrasound and drugs to which pregnant women may be exposed, e.g. nicotine, alcohol, tranquilizers, tocolytic agents. A subset of the basic experiments described above will be replicated adding another experimental group: cells and blastocysts exposed to both ultrasound and drugs. From these pilot studies we will determine: 1) which drugs seem most promising for future experiments; 2) which biological endpoints are the most sensitive indicators of biological damage; 3) what sample sizes would be required to reach statistical significance. Effects of ultrasound on abnormal cell lines will also be explored.